Overcoming Delays in the Progress against Cancer: Identifying Tobacco Use among Cancer Patients Enrolled in Clinical Trials.

Though smoking causes adverse cancer treatment outcomes and smoking cessation can improve survival, prior literature demonstrates deficits in collecting tobacco use information in clinical trials. Results by Streck and colleagues represent a thorough structured assessment of tobacco use and alternative tobacco product use in patients enrolled in cooperative group trials. Among patients with predominantly non-tobacco related cancers, observations demonstrate that approximately 27% of patients reported using one or more forms of tobacco use after diagnosis. Alternative tobacco use was reported by many patients, including patterns of dual use. Results demonstrate the feasibility of collecting comprehensive structured tobacco use information, and further support the need to address tobacco and cessation even among patients with non-tobacco related cancers. See related article by Streck and colleagues, Cancer Epidemiol Biomarkers Prev 2023;32:1552-57.

Overcoming Barriers to Tobacco Cessation and Lung Cancer Screening among Racial and Ethnic Minority Groups and Underserved Patients in Academic Centers and Community Network Sites: The City of Hope Experience.

BACKGROUND: Tobacco control is important for cancer patient health, but delivering effective low-dose CT (LDCT) screening and tobacco cessation is more difficult in underserved and patients from racial and ethnic minority groups. At City of Hope (COH), we have developed strategies to overcome barriers to the delivery of LDCT and tobacco cessation. METHODS: We performed a needs assessment. New tobacco control program services were implemented focusing on patients from racial and ethnic minority groups. Innovations included Whole Person Care with motivational counseling, placing clinician and nurse champions at points of care, training module and leadership newsletters, and a patient-centric personalized medicine Personalized Pathways to Success (PPS) program. RESULTS: Emphasis on patients from racial and ethnic minority groups was implemented by training cessation personnel and lung cancer control champions. LDCT increased. Tobacco use assessment increased and abstinence was 27.2%. The PPS pilot program achieved 47% engagement in cessation, with self-reported abstinence at 3 months of 38%, with both results slightly higher in patients from racial and ethnic minority groups than in Caucasian patients. CONCLUSIONS: Tobacco cessation barrier-focused innovations can result in increased lung cancer screening and tobacco cessation reach and effectiveness, especially among patients from racial and ethnic minority groups. The PPS program is promising as a personalized medicine patient-centric approach to cessation and lung cancer screening.

Increasing clinician participation in tobacco cessation by an implementation science-based tobacco cessation champion program.

BACKGROUND: We designed a process to increase tobacco cessation in an academic center and its widely distributed network community sites using clinical champions to overcome referral barriers. METHODS: In 2020 a needs assessment was performed across the City of Hope Medical Center and its 32 community treatment sites. We reviewed information science strategies to choose elements for our expanded tobacco control plan, focusing on distributed leadership with tobacco cessation champions. We analyzed smoking patterns in patients with cancer before and following program implementation. We evaluated the champion experience and measured tobacco abstinence after 6 months of follow-up. RESULTS: Cancer center leadership committed to expanding tobacco control. Funding was obtained through a Cancer Center Cessation Initiative (C3I) grant. Multi-disciplinary leaders developed a comprehensive plan. Disease-focused clinics and community sites named cessation champions (a clinician and nurse) supported by certified tobacco treatment specialists. Patient, staff, clinician, and champion training/education were developed. Roles and responsibilities of the champions were defined. Implementation in pilot sites showed increased tobacco assessment from 80.8 to 96.6%, increased tobacco cessation referral by 367%, and moderate smoking abstinence in both academic (27.2%) and community sites (22.5%). 73% of champions had positive attitudes toward the program. CONCLUSION: An efficient process to expand smoking cessation in the City of Hope network was developed using implementation science strategies and cessation champions. This well-detailed implementation process may be helpful to other cancer centers, particularly those with a tertiary care cancer center and community network.

The Impact of the COVID-19 Pandemic on Tobacco Treatment Program Implementation at National Cancer Institute-Designated Cancer Centers.

INTRODUCTION: The COVID-19 pandemic disrupted cancer screening and treatment delivery, but COVID-19's impact on tobacco cessation treatment for cancer patients who smoke has not been widely explored. AIMS AND METHODS: We conducted a sequential cross-sectional analysis of data collected from 34 National Cancer Institute (NCI)-designated cancer centers participating in NCI's Cancer Center Cessation Initiative (C3I), across three reporting periods: one prior to COVID-19 (January-June 2019) and two during the pandemic (January-June 2020, January-June 2021). Using McNemar's Test of Homogeneity, we assessed changes in services offered and implementation activities over time. RESULTS: The proportion of centers offering remote treatment services increased each year for Quitline referrals (56%, 68%, and 91%; p = .000), telephone counseling (59%, 79%, and 94%; p = .002), and referrals to Smokefree TXT (27%, 47%, and 56%; p = .006). Centers offering video-based counseling increased from 2020 to 2021 (18% to 59%; p = .006), Fewer than 10% of centers reported laying off tobacco treatment staff. Compared to early 2020, in 2021 C3I centers reported improvements in their ability to maintain staff and clinician morale, refer to external treatment services, train providers to deliver tobacco treatment, and modify clinical workflows. CONCLUSIONS: The COVID-19 pandemic necessitated a rapid transition to new telehealth program delivery of tobacco treatment for patients with cancer. C3I cancer centers adjusted rapidly to challenges presented by the pandemic, with improvements reported in staff morale and ability to train providers, refer patients to tobacco treatment, and modify clinical workflows. These factors enabled C3I centers to sustain evidence-based tobacco treatment implementation during and beyond the COVID-19 pandemic. IMPLICATIONS: This work describes how NCI-designated cancer centers participating in the Cancer Center Cessation Initiative (C3I) adapted to challenges to sustain evidence-based tobacco use treatment programs during the COVID-19 pandemic. This work offers a model for resilience and rapid transition to remote tobacco treatment services delivery and proposes a policy and research agenda for telehealth services as an approach to sustaining evidence-based tobacco treatment programs.

Integrating Tobacco Treatment Into Oncology Care: Reach and Effectiveness of Evidence-Based Tobacco Treatment Across National Cancer Institute-Designated Cancer Centers.

PURPOSE: Quitting smoking improves patients' clinical outcomes, yet smoking is not commonly addressed as part of cancer care. The Cancer Center Cessation Initiative (C3I) supports National Cancer Institute-designated cancer centers to integrate tobacco treatment programs (TTPs) into routine cancer care. C3I centers vary in size, implementation strategies used, and treatment approaches. We examined associations of these contextual factors with treatment reach and smoking cessation effectiveness. METHODS: This cross-sectional study used survey data from 28 C3I centers that reported tobacco treatment data during the first 6 months of 2021. Primary outcomes of interest were treatment reach (reach)-the proportion of patients identified as currently smoking who received at least one evidence-based tobacco treatment component (eg, counseling and pharmacotherapy)-and smoking cessation effectiveness (effectiveness)-the proportion of patients reporting 7-day point prevalence abstinence at 6-month follow-up. Center-level differences in reach and effectiveness were examined by center characteristics, implementation strategies, and tobacco treatment components. RESULTS: Of the total 692,662 unique patients seen, 44,437 reported current smoking. Across centers, a median of 96% of patients were screened for tobacco use, median smoking prevalence was 7.4%, median reach was 15.4%, and median effectiveness was 18.4%. Center-level characteristics associated with higher reach included higher smoking prevalence, use of center-wide TTP, and lower patient-to-tobacco treatment specialist ratio. Higher effectiveness was observed at centers that served a larger overall population and population of patients who smoke, reported a higher smoking prevalence, and/or offered electronic health record referrals via a closed-loop system. CONCLUSION: Whole-center TTP implementation among inpatients and outpatients, and increasing staff-to-patient ratios may improve TTP reach. Designating personnel with tobacco treatment expertise and resources to increase tobacco treatment dose or intensity may improve smoking cessation effectiveness.

Tragic Triad of Tobacco Dependence, Cancer, and COVID-19 Pandemic: An Urgent Call for Attention by Health Care Systems and Professionals.

Tobacco smoke is a well-known carcinogen associated with multiple malignancies. Patients with cancer, as well as survivors, who continue to smoke are at a greater risk for poor cancer treatment outcomes. With the emergence of the COVID-19 pandemic, there is increased frequency and severity of the infection in patients with cancer. Furthermore, smoking and/or vaping increases incidence or likelihood of progression of COVID-19. Cigarette smoking, cancer, and COVID-19 each impose disproportionate burden of illness and death among racial and ethnic minorities. Geographic and population-specific analyses reveal that neighborhoods with lower income and higher minority populations have more tobacco/vape shops and face increased risk associated with tobacco marketing. Referral to tobacco cessation has been reduced during the pandemic. To reduce the adverse health effects of tobacco dependence among patients with cancer during the pandemic, urgent evidence-based solutions are described for health systems and professionals to prioritize tobacco cessation for patients with cancer in the midst of the COVID-19 pandemic, on the basis of cessation implementation at City of Hope Medical Center.

Phase II study of neratinib in older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer.

OBJECTIVE: The tolerability and efficacy of targeted therapy in older adults with cancer has not been adequately studied. Neratinib is a novel HER1, HER2, HER4 tyrosine kinase inhibitor that has recently been granted FDA approval for treatment of breast cancer. The major toxicity of neratinib is diarrhea, which affects up to 90% of patients. This phase II trial evaluates the safety and tolerability of neratinib in adults ≥60. METHODS: Patients aged 60 or older with histologically proven metastatic breast cancer and HER2 amplification (defined by ASCO/CAP guideline) or HER2/HER3 activating mutation were enrolled to receive neratinib at 240 mg daily in 28-day cycles. The association between tolerability, defined as dose reduction and number of completed courses, and log2 Cancer and Aging Research Group (CARG) toxicity risk score was assessed using a Student's t-test and linear regression, respectively. Response rate, progression free survival, and overall survival were also evaluated. RESULTS: 25 patients were enrolled with median age of 66 (range 60-79). Seventy-six percent of patients were white, 16% Asian, and 8% African-American. Seventy-six percent were patients with hormone receptor (HR) positive metastatic breast cancer (MBC) and 24% were patients with HR negative MBC. Median number of prior lines of metastatic therapy were 3 (range 0-11). 20/25 (80%) had worst grade toxicities ≥2. A total of 9/25 (36%) had grade 3 toxicities including 5/20 (20%) diarrhea, 2/20 (8%) vomiting, and 2/20 (8%) abdominal pain. There were no grade 4 or 5 toxicities. A total of 9/25 (36%) had dose reduction, and 2/25 (8%) discontinued therapy due to toxicity. The association between dose reductions and CARG toxicity score reached borderline statistical significance suggesting a trend with participants with higher CARG toxicity risk scores being more likely to require a dose modification (p = 0.054). 1/25 (4%) had a partial response, 11/25 (44%) had stable disease, 12/25 (48%) had progression of disease, and 1/25 (4%) was not assessed. Median progression free survival (PFS) was 2.6 months (95% CI [2.56-5.26]), and median overall survival (OS) was 17.4 months (95% CI [10.3, NA]). CONCLUSIONS: Neratinib was safe in this population of older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer (BC). Higher CARG toxicity risk score may be associated with greater need for dose adjustments. Future studies are needed to confirm this finding.

Implementing Lung Cancer Screening and Prevention in Academic Centers, Affiliated Network Offices and Collaborating Care Sites.

Lung cancer is one of the deadliest and yet largely preventable neoplasms. Smoking cessation and lung cancer screening are effective yet underutilized lung cancer interventions. City of Hope Medical Center, a National Cancer Institute (NCI)- designated comprehensive cancer center, has 27 community cancer centers and has prioritized tobacco control and lung cancer screening throughout its network. Despite challenges, we are implementing and monitoring the City of Hope Tobacco Control Initiative including 1) a Planning and Implementation Committee; 2) integration of IT, e.g., medical records and clinician notification/prompts to facilitate screening, cessation referral, and digital health, e.g., telehealth and social media; 3) clinician training and endorsing national guidelines; 4) providing clinical champions at all sites for site leadership; 5) Coverage and Payment reform and aids to facilitate patient access and reduce cost barriers; 6) increasing tobacco exposure screening for all patients; 7) smoking cessation intervention and evaluation-patient-centered recommendations for smoking cessation for all current and recent quitters along with including QuitLine referral for current smokers and smoking care-givers; and 8) establishing a Tobacco Registry for advancing science and discoveries including team science for basic, translation and clinical studies. These strategies are intended to inform screening, prevention and treatment research and patient-centered care.

Application of a drug-induced apoptosis assay to identify treatment strategies in recurrent or metastatic breast cancer.

BACKGROUND: A drug-induced apoptosis assay has been developed to determine which chemotherapy drugs or regimens can produce higher cell killing in vitro. This study was done to determine if this assay could be performed in patients with recurrent or metastatic breast cancer patients, to characterize the patterns of drug-induced apoptosis, and to evaluate the clinical utility of the assay. A secondary goal was to correlate assay use with clinical outcomes. METHODS: In a prospective, non-blinded, multi institutional controlled trial, 30 evaluable patients with recurrent or metastatic breast cancer who were treated with chemotherapy had tumor samples submitted for the MiCK drug-induced apoptosis assay. After receiving results within 72 hours after biopsy, physicians could use the test to determine therapy (users), or elect to not use the test (non-users). RESULTS: The assay was able to characterize drug-induced apoptosis in tumor specimens from breast cancer patients and identified which drugs or combinations gave highest levels of apoptosis. Patterns of drug activity were also analyzed in triple negative breast cancer. Different drugs from a single class of agents often produced significantly different amounts of apoptosis. Physician frequently (73%) used the assay to help select chemotherapy treatments in patients, Patients whose physicians were users had a higher response (CR+PR) rate compared to non-users (38.1% vs 0%, p = 0.04) and a higher disease control (CR+PR+Stable) rate (81% vs 25%, p<0.01). Time to relapse was longer in users 7.4 mo compared to non-users 2.2 mo (p<0.01). CONCLUSIONS: The MiCK assay can be performed in breast cancer specimens, and results are often used by physicians in breast cancer patients with recurrent or metastatic disease. These results from a good laboratory phase II study can be the basis for a future larger prospective multicenter study to more definitively establish the value of the assay. TRIAL REGISTRATION: Clinicaltrials.gov NCT00901264.

Correlation of the microculture-kinetic drug-induced apoptosis assay with patient outcomes in initial treatment of adult acute myelocytic leukemia.

Overall survival (OS) with acute myeloid leukemia (AML) remains poor. Determining prognostic factors will help in selecting patients for appropriate treatments. Our aim was to determine whether the level of drug-induced apoptosis (chemosensitivity) demonstrated by the microculture-kinetic drug-induced apoptosis (MiCK) assay significantly predicted outcomes after standard AML induction therapy. A total of 109 patients with untreated AML had blood and/or bone marrow aspirate samples analyzed for anthracycline-induced apoptosis using the MiCK assay. The amount of apoptosis observed over 48 h was determined and expressed as kinetic units of apoptosis (KU). Complete remission (CR) was significantly higher (72%) in patients with high idarubicin-induced apoptosis >3 KU compared to patients with apoptosis ≤ 3 KU (p = 0.01). Multivariate analysis showed the only significant variables to be idarubicin-induced apoptosis and karyotype. Median overall survival of patients with idarubicin-induced apoptosis >3 KU was 16.1 months compared to 4.5 months in patients with apoptosis ≤ 3 KU (p = 0.004). Multivariate analysis showed the only significant variable to be idarubicin-induced apoptosis. Chemotherapy-induced apoptosis measured by the MiCK assay demonstrated significant correlation with outcomes and appears predictive of complete remission and overall survival for patients receiving standard induction chemotherapy.

The microculture-kinetic (MiCK) assay: the role of a drug-induced apoptosis assay in drug development and clinical care.

A drug-induced apoptosis assay, termed the microculture-kinetic (MiCK) assay, has been developed. Blinded clinical trials have shown higher response rates and longer survival in groups of patients with acute myelocytic leukemia and epithelial ovarian cancer who have been treated with drugs that show high apoptosis in the MiCK assay. Unblinded clinical trials in multiple tumor types have shown that the assay will be used frequently by clinicians to determine treatment, and when used, results in higher response rates, longer times to relapse, and longer survivals. Model economic analyses suggest possible cost savings in clinical use based on increased generic drug use and single-agent substitution for combination therapies. Two initial studies with drugs in development are promising. The assay may help reduce costs and speed time to drug approval. Correlative studies with molecular biomarkers are planned. This assay may have a role both in personalized clinical therapy and in more efficient drug development.

Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response.

BACKGROUND: This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK) could predict the best therapy for patients with ovarian cancer. METHODS: A prospective, multi-institutional and blinded trial of the assay was conducted in 104 evaluable ovarian cancer patients treated with chemotherapy. The MiCK assay was performed prior to therapy, but treating physicians were not told of the results and selected treatment only on clinical criteria. Outcomes (response, time to relapse, and survival) were compared to the drug-induced apoptosis observed in the assay. RESULTS: Overall survival in primary therapy, chemotherapy naïve patients with Stage III or IV disease was longer if patients received a chemotherapy which was best in the MiCK assay, compared to shorter survival in patients who received a chemotherapy that was not the best. (p < 0.01, hazard ratio HR 0.23). Multivariate model risk ratio showed use of the best chemotherapy in the MiCK assay was the strongest predictor of overall survival (p < 0.01) in stage III or IV patients. Standard therapy with carboplatin plus paclitaxel (C + P) was not the best chemotherapy in the MiCK assay in 44% of patients. If patients received C + P and it was the best chemotherapy in the MiCK assay, they had longer survival than those patients receiving C + P when it was not the best chemotherapy in the assay (p = 0.03). Relapse-free interval in primary therapy patients was longer if patients received the best chemotherapy from the MiCK assay (p = 0.03, HR 0.52). Response rates (CR + PR) were higher if physicians used an active chemotherapy based on the MiCK assay (p = 0.03). CONCLUSION: The MiCK assay can predict the chemotherapy associated with better outcomes in ovarian cancer patients. This study quantifies outcome benefits on which a prospective randomized trial can be developed.

Correlation of drug-induced apoptosis assay results with oncologist treatment decisions and patient response and survival.

BACKGROUND: An observational prospective nonblinded clinical trial was performed to determine the effect of a drug-induced apoptosis assay results on treatments planned by oncologists. METHODS: Purified cancer cells from patient biopsies were placed into the MiCK (Microculture Kinetic) assay, a short-term culture, which determined the effects of single drugs or combinations of drugs on tumor cell apoptosis. An oncologist received the assay results before finalizing the treatment plan. Use of the MiCK assay was evaluated and correlated with patient outcomes. RESULTS: Forty-four patients with successful MiCK assays from breast cancer (n = 16), nonsmall cell lung cancer (n = 6), non-Hodgkin lymphoma (n = 4), and others were evaluated. Four patients received adjuvant chemotherapy after MiCK, and 40 received palliative chemotherapy with a median line of therapy of 2. Oncologists used the MiCK assay to determine chemotherapy (users) in 28 (64%) and did not (nonusers) in 16 patients (36%). In users receiving palliative chemotherapy, complete plus partial response rate was 44%, compared with 6.7% in nonusers (P < .02). The median overall survival was 10.1 months in users versus 4.1 months in nonusers (P = .02). Relapse-free interval was 8.6 months in users versus 4.0 months in nonusers (P < .01). CONCLUSIONS: MiCK assay results are frequently used by oncologists. Outcomes appear to be statistically superior when oncologists use chemotherapy based on MiCK assay results compared with when they do not use the assay results. When available to oncologists, MiCK assay results help to determine patient treatment plans.

A copay foundation assistance support program for patients receiving intravenous cancer therapy.

PURPOSE: With the advent of newer cancer therapies (eg, biologic and cytotoxic), treatment is becoming increasingly expensive for patients with cancer. Patients enrolled in Medicare and commercial insurance plans often have large copay requirements with each treatment cycle. Often, these patients undergo significant financial hardship, and some patients decline treatment. We have developed a support program that works closely with all copay assistance foundations to secure financial assistance to facilitate appropriate treatment. METHODS: In September, 2008 we initiated a coordinated program with various copay assistance foundations, including Healthwell, Cancer Care, Patient Access, Chronic Disease Fund, Beckstrand Cancer, Lilly Cares and the Leukemia and Lymphoma Society. Patients requesting assistance with chemotherapy copay were enrolled in this program. Information about income level, chemotherapy regimens, and associated copay was given to these foundations, who then determined the amount of monetary assistance. RESULTS: Since the initiation of this program, of 201 patients who began receiving chemotherapy, 25 (12.4%) requested assistance with this program for either intravenous or oral treatments. The current results of time delays for foundation decision, success rates and administrative costs to secure funding will be presented at the time of the poster presentation. CONCLUSION: Copay for chemotherapy drugs is a financial hardship for a significant number of patients. Coordinated resources must be provided and reimbursed to facilitate appropriate and sustainable cancer care. This program is a successful model for other centers to adopt.

Endometrial carcinoma in vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic apoptosis assay: implications for endometrial cancer treatment.

OBJECTIVE: The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. METHODS: Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. RESULTS: Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. CONCLUSION: Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.

Aromatase inhibitor-associated arthralgia and/ or bone pain: frequency and characterization in non-clinical trial patients.

BACKGROUND: The frequency of aromatase inhibitor (AI)-associated arthralgia and/or bone pain in clinical practice is not known. PATIENTS AND METHODS: Fifty-six consecutive patients with breast cancer not on clinical trials who were receiving AIs in a clinical practice were interviewed regarding occurrence of worsening or new arthralgia and/or bone pain after starting AI therapy. The occurrence, character, severity, and resolution of pain were evaluated. RESULTS: Arthralgia and/or bone pain was reported in 61% of patients. It was severe in 30%, continuous in 41%, central in 50%, peripheral in 79%, and resulted in discontinuation of the drug in 20% of patients. Effective therapies in controlling pain were acetaminophen, 29%; nonsteroidal anti-inflammatory drugs, 50%; opiates, 18%, and glucosamine in 15% of patients. Despite this, 20% of patients discontinued AI therapy because of pain. CONCLUSION: Aromatase inhibitor-associated pain is more frequent in patients not in clinical trials than previously appreciated in clinical trials. Improved patient education is needed, and prompt therapeutic management of pain is required to ensure continued drug treatment and improved quality of life.

Effects of weekly paclitaxel or paclitaxel plus carboplatin on functionality and symptoms of geriatric patients with cancer as measured by a brief geriatric oncology module: a pilot experience.

BACKGROUND: To measure functionality, symptoms, and quality of life in elderly patients, a geriatric oncology module (GOM) was developed that could be rapidly and effectively administered in community oncology practices. METHODS: The GOM was validated by semi structured patient interviews. The authors tested 26 patients receiving chemotherapy with paclitaxel or paclitaxel plus carboplatin to determine the effect of drug treatment on functionality, symptoms, and quality of life (QOL). RESULTS: Chemotherapy stabilized or improved functionality, symptoms, and QOL in 75%, 86%, and 76% of patients, respectively. This GOM was easily implemented in a busy community oncology practice. CONCLUSIONS: Weekly paclitaxel and paclitaxel plus carboplatin produced measurable palliation in geriatric oncology patients. This GOM may be useful in the assessment of specific chemotherapeutic interventions in elderly patients with cancer in community oncology practices.

Does leucovorin alter the intratumoral pharmacokinetics of 5-fluorouracil (5-FU)? A Southwest Oncology Group study.

PURPOSE AND DESIGN: We previously documented that there was an association between the intra-tumoral pharmacokinetics (TPK) of 5-FU and response to therapy with 5-FU and leucovorin (p < .0001). Since we have shown that other modulators of 5-FU, such as methotrexate, interferon and neutrexin alter its TPK, it was of interest to determine if the modulating effect of leucovorin would also alter the tumoral PK of 5-FU. In order to determine the effect of leucovorin on intratumoral 5-FU pharmacokinetics, 23 patients (21 evaluable) underwent 19F magnetic resonance spectroscopy (19F-MRS) twice. The first 19F-MRS was following 5-FU 600 mg/m2 alone, and the second 19F-MRS was following by leucovorin 500 mg/m2 and then 5-FU 600 mg/m2. RESULTS: A comparison of the intratumoral 5-FU pharmacokinetics indicated that there was no general effect of leucovorin on the intratumoral half-life of 5-FU. In only two of these 21 patients was the half-life of 5-FU altered, and in both cases it was decreased by more than 20%. Partial responses to 5-FU plus leucovorin therapy were seen only in patients with a long intratumoral half-life (trapping) of 5-FU (3 PR in 11 patients with T1/2 > or = 20 minutes, compared to 0 PR in 11 patients with T1/2 < 20 minutes). There was a statistically significant correlation between tumor response and the intratumoral T1/2 of 5-FU, consistent with our prior results in a larger number of patients. However, there was no statistically significant correlation of time-to-progression or survival with classification of the patients into trappers or non-trappers, probably due to the small sample size in this current study. CONCLUSION: The data reported here are compatible with the hypothesis that leucovorin enhancement of 5-fluorouracil antitumor responses is not mediated by the levels of 5-FU in tumors, but rather, is due to the modulation by leucovorin of cellular metabolic processes that follow the uptake of free 5-FU into the tumor cell. The MRS technique may be useful in selected instances for elucidating the possible metabolic interactions of drugs in vivo.